Expansion of chondroprogenitor cells on macroporous microcarriers as an alternative to conventional monolayer systems.

Routine tissue culture methodologies can hardly cope with the scale of cell production required for the manufacture of engineered cartilage tissue products. In vitro cell expansion has become an essential step in the process of tissue engineering of articular cartilage and the optimization of expansion protocols is a fundamental issue that needs to be addressed. The expansion suitability of chondroprogenitor cells isolated from the superficial zone of articular cartilages was evaluated in both conventional monolayer and macroporous microcarrier in spinner flask cultures. Although monolayer systems promoted rapid in vitro expansion of undifferentiated cells, they present limited scalability. Alternatively, the use of CultiSpher-G microcarriers resulted in cell densities of 5.5 x 10(5) cell/ml, representing a 17-fold expansion in batch cultures. In addition, chondroprogenitor cells were capable of undergoing bead-to-bead migration, which allowed subcultivation to be performed without a harvesting step, thus improving the scalability of the expansion process. By employing macroporous microcarrier cultures it will be possible to obtain large number of chondroprogenitor cells for tissue engineering applications. Not only its satisfactory expansion potential, but more importantly the cost and operational advantages over traditional monolayer culture make this system a feasible alternative method for the extensive expansion of chondroprogenitor cells.

Use of Disinfection Cap to Reduce Central-Line-Associated Bloodstream Infection and Blood Culture Contamination Among Hematology-Oncology Patients.

OBJECTIVE: In this study, we examined the impact of routine use of a passive disinfection cap for catheter hub decontamination in hematology-oncology patients. SETTING: A tertiary care cancer center in New York City. METHODS: In this multiphase prospective study, we used 2 preintervention phases (P1 and P2) to establish surveillance and baseline rates followed by sequential introduction of disinfection caps on high-risk units (HRUs: hematologic malignancy wards, hematopoietic stem cell transplant units and intensive care units) (P3) and general oncology units (P4). Unit-specific and hospital-wide hospital-acquired central-line-associated bloodstream infection (HA-CLABSI) rates and blood culture contamination (BCC) with coagulase negative staphylococci (CONS) were measured. RESULTS: Implementation of a passive disinfection cap resulted in a 34% decrease in hospital-wide HA-CLABSI rates (combined P1 and P2 baseline rate of 2.66-1.75 per 1,000 catheter days at the end of the study period). This reduction occurred only among high-risk patients and not among general oncology patients. In addition, the use of the passive disinfection cap resulted in decreases of 63% (HRUs) and 51% (general oncology units) in blood culture contamination, with an estimated reduction of 242 BCCs with CONS. The reductions in HA-CLABSI and BCC correspond to an estimated annual savings of $3.2 million in direct medical costs. CONCLUSION: Routine use of disinfection caps is associated with decreased HA-CLABSI rates among high-risk hematology oncology patients and a reduction in blood culture contamination among all oncology patients.

Incidence of tuberculosis and survival after its diagnosis in patients infected with HIV-1 and HIV-2.

BACKGROUND: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival. OBJECTIVE: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type. METHODS: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l. RESULTS: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7). CONCLUSION: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.

Practically speaking: rethinking hand hygiene improvement programs in health care settings.

BACKGROUND: Hand hygiene is widely recognized as the single most effective means of reducing health care-associated infections. Implementing a credible hand hygiene program and maintaining high compliance among staff is both expected and required of hospitals. However, beyond general guidelines, few resources are available for establishing an institution-wide hand hygiene program that is both successful and sustainable over the long term. METHODS: Beginning in 2008, we completely overhauled the approach to hand hygiene at our institution. We created small teams consisting of a representative from Quality Assessment, an Infection Prevention Practitioner, and staff from a particular unit. Teams began by discussing the current barriers to hand hygiene success. They then set their own goals for hand hygiene compliance. Staff learned the World Health Organization (WHO) hand hygiene guidelines, which recently had been adopted as part of hospital infection prevention policy. Using the WHO guidelines, teams diagrammed detailed workflows for several of their most common patient care tasks. Wherever hand hygiene was indicated, the workflow was marked with a number corresponding to one or more of the WHO's "5 moments for hand hygiene." At the end of the 12-week period, staff members were trained to observe each other and began officially collecting and submitting data to Infection Prevention. RESULTS: Between 2006 and 2008, our average institutional hand hygiene compliance held steady at 60%-70%. After the new program was launched in 2008, compliance reached 97% and has been maintained at this level ever since. In addition to the 19 areas of the hospital that were observed previously, 15 ambulatory facilities and 5 regional sites are now included in the data. CONCLUSION: This article describes a novel approach to measuring, monitoring, and ultimately increasing hand hygiene compliance at our hospital. Our objective is to provide concrete, practical strategies for other institutions faced with the challenge of building or revamping their own hand hygiene programs.

Optimal in-vitro expansion of chondroprogenitor cells in monolayer culture.

A continuous production of large quantities of chondroprogenitor cells for the manufacture of engineered cartilage tissue products is required. Expansion of the cell population in vitro has become an essential step in the process of tissue engineering of articular cartilage and the optimization of the culture conditions is a fundamental problem that needs to be addressed. The analysis of both seeding density and passage length was considered crucial in the optimization of expansion processes, and their correct selection should be taken as a requisite to establish culture conditions for monolayer systems. The determination of the optimal seeding density and the corresponding passage length for cell expansion in a serial passaging operation was found to be a compromise between growth kinetics and process time. This optimal determination was carried out using a mathematical approach that led to values of 10(4) cell/cm(2) for seeding density and 73 h for passage length. Additional considerations concerning the running cost of the process were introduced. Although the optimal passage length gave the desired expansion factor in a minimum process time, the selection of an alternative value of 120 h was shown to reduce the cost of the expansion process in more than 60%. The optimization approach presented will contribute to the development of feasible large scale expansion operations of chondroprogenitor cells required by the cartilage tissue engineering industry.